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1. 发明授权

US5650148A Method of grafting genetically modified cells to treat defects, disease or damage of the central nervous system 失效
标题翻译：遗传修饰细胞移植治疗中枢神经系统缺陷，疾病或损害的方法
公开(公告)号：US5650148A
公开(公告)日：1997-07-22
申请号：US209609
申请日：1994-03-10
申请人： Fred H. Gage , Theodore Friedmann , Michael B. Rosenberg , Jon A. Wolff , Malcolm Schinstine , Michael D. Kawaja , Jasodhara Ray
发明人： Fred H. Gage , Theodore Friedmann , Michael B. Rosenberg , Jon A. Wolff , Malcolm Schinstine , Michael D. Kawaja , Jasodhara Ray
IPC分类号： A61K38/18 , A61K38/44 , A61K48/00 , C12N9/10 , A61K31/00 , C12N5/00 , C12N15/00
CPC分类号： C12N9/1029 , A61K35/33 , A61K38/13 , A61K38/1808 , A61K38/1825 , A61K38/185 , A61K38/44 , C12N9/1077 , C12Y114/16002 , C12Y203/01006 , A61K38/00 , A61K48/00 , Y10S435/948
摘要： Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat defective, diseased or damaged cells are disclosed. The modified donor cells produce functional molecules that effect the recovery or improved function of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.
摘要翻译：公开了通过基因转移遗传修饰供体细胞用于接枝入中枢神经系统以治疗有缺陷的，患病或损伤的细胞的方法。修饰的供体细胞产生影响CNS细胞恢复或改善功能的功能性分子。描述了用于进行基因转移和接枝的方法和载体。

2. 发明授权

US5762926A Method of grafting genetically modified cells to treat defects, disease or damage of the central nervous system 失效
标题翻译：遗传修饰细胞移植治疗中枢神经系统缺陷，疾病或损害的方法
公开(公告)号：US5762926A
公开(公告)日：1998-06-09
申请号：US464397
申请日：1995-06-05
申请人： Fred H. Gage , Malcolm Schinstine , Jasodhara Ray , Theodore Friedmann , Michael D. Kawaja , Michael B. Rosenberg , Jon A. Wolff
发明人： Fred H. Gage , Malcolm Schinstine , Jasodhara Ray , Theodore Friedmann , Michael D. Kawaja , Michael B. Rosenberg , Jon A. Wolff
IPC分类号： A61K38/18 , A61K38/44 , A61K48/00 , C12N9/10 , C12N5/00 , C12N15/09 , C12N15/79
CPC分类号： C12N9/1029 , A61K35/33 , A61K38/13 , A61K38/1808 , A61K38/1825 , A61K38/185 , A61K38/44 , C12N9/1077 , C12Y114/16002 , C12Y203/01006 , A61K38/00 , A61K48/00 , Y10S435/948
摘要： Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat defective, diseased or damaged cells are disclosed. The modified donor cells produce functional molecules that effect the recovery or improved function of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.
摘要翻译：公开了通过基因转移遗传修饰供体细胞用于接枝入中枢神经系统以治疗有缺陷的，患病或损伤的细胞的方法。修饰的供体细胞产生影响CNS细胞恢复或改善功能的功能性分子。描述了用于进行基因转移和接枝的方法和载体。

3. 发明授权

US5082670A Method of grafting genetically modified cells to treat defects, disease or damage or the central nervous system 失效
标题翻译：研究遗传改良细胞治疗缺陷，疾病或损害或中枢神经系统的方法
公开(公告)号：US5082670A
公开(公告)日：1992-01-21
申请号：US285196
申请日：1988-12-15
申请人： Fred H. Gage , Michael B. Rosenberg , Theodore Friedmann
发明人： Fred H. Gage , Michael B. Rosenberg , Theodore Friedmann
IPC分类号： A61K35/12 , A61K38/00 , A61K38/18 , A61K38/44 , A61K48/00 , C07K14/48 , C12N9/02 , C12N9/10 , C12N15/867
CPC分类号： C12N15/86 , A61K38/1825 , A61K48/00 , C07K14/48 , C12N9/0071 , C12N9/1029 , C12Y114/16002 , A61K38/00 , C12N2740/13043 , Y10S435/948
摘要： Methods of genetically modifying donor cells by gene transfer for grafting into the central nervous system to treat diseased or damaged cells are disclosed. The modified donor cells produce a molecule capable of affecting the recovery of cells in the CNS. Methods and vectors for carrying out gene transfer and grafting are described.
摘要翻译：公开了通过基因转移遗传修饰供体细胞用于接枝入中枢神经系统以治疗患病或受损细胞的方法。修饰的供体细胞产生能够影响CNS细胞恢复的分子。描述了用于进行基因转移和接枝的方法和载体。

4. 发明授权

US5674486A Cancer immunotherapy with carrier cells 失效
标题翻译：用载体细胞进行癌症免疫治疗
公开(公告)号：US5674486A
公开(公告)日：1997-10-07
申请号：US473123
申请日：1995-06-06
申请人： Robert E. Sobol , Fred H. Gage , Ivor Royston , Theodore Friedmann
发明人： Robert E. Sobol , Fred H. Gage , Ivor Royston , Theodore Friedmann
IPC分类号： A61K38/19 , A61K38/20 , A61K39/00 , A61K48/00 , A61K35/76 , C12N5/00
CPC分类号： A61K38/2013 , A61K39/0011 , A61K48/00
摘要： A novel method of tumor immunotherapy is described comprising the genetic modification of cells resulting in the secretion of cytokine gene products to stimulate a patient's immune response to tumor antigens. In one embodiment, autologous fibroblasts genetically modified to secrete at least one cytokine gene product are utilized to immunize the patient in a formulation with tumor antigens at a site other than an active tumor site. In another embodiment, cells genetically modified to express at least one tumor antigen gene product and to secrete at least one cytokine gene product are utilized in a formulation to immunize the patient at a site other than an active tumor site.
摘要翻译：描述了一种新的肿瘤免疫治疗方法，其包括导致分泌细胞因子基因产物以刺激患者对肿瘤抗原的免疫应答的细胞的遗传修饰。在一个实施方案中，利用经遗传修饰以分泌至少一种细胞因子基因产物的自体成纤维细胞在具有肿瘤抗原的制剂中在除活性肿瘤部位之外的部位免疫患者。在另一个实施方案中，在制剂中利用遗传修饰以表达至少一种肿瘤抗原基因产物并分泌至少一种细胞因子基因产物的细胞，以在除活性肿瘤部位之外的部位免疫患者。

5. 发明授权

US5670354A Use of VSV-G pseudotyped vectors for transfer of genes into embryos 失效
标题翻译：使用VSV-G假型载体将基因转移到胚胎中
公开(公告)号：US5670354A
公开(公告)日：1997-09-23
申请号：US480453
申请日：1995-06-07
申请人： Jane C. Burns , Jiing-Kuan Yee , Theodore Friedmann
发明人： Jane C. Burns , Jiing-Kuan Yee , Theodore Friedmann
IPC分类号： C12N5/00 , A61K38/00 , A61K48/00 , C07K14/145 , C12N5/10 , C12N7/00 , C12N7/04 , C12N15/09 , C12N15/867 , C12N15/87 , C12R1/91 , C12N15/00 , C12N5/06 , C12N5/16 , C12N15/06
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C12N15/87 , C12N7/00 , A61K38/00 , C12N2740/13043 , C12N2740/13052 , C12N2740/13062 , C12N2760/20222 , C12N2830/002 , C12N2830/42 , C12N2830/60 , C12N2840/20 , C12N2840/203
摘要： The present application discloses retrovirus-derived vectors in which the retroviral envelope glycoprotein has been replaced by the G glycoprotein of vesicular stomatitis virus, and the use of these vectors in the transfer of exogenous genes into the cells of a wide variety of non-mammalian organisms. Also disclosed is a method for the generation of retroviral vectors in high titers, wherein a recombinant, stable host cell line is provided which harbors the retroviral vector of interest without envelope protein. High-titer retroviral vector production is initiated by introducing nucleic acid encoding a functional membrane-associated protein into the cell line. The vectors disclosed in the present application can be concentrated by ultracentrifugation to titers greater than 10.sup.9 cfu/ml which are especially useful in human gene therapy trials, and can also infect cells, such as hamster and fish cells, that are ordinarily resistant to infection with vectors containing the retroviral envelope protein.
摘要翻译：本申请公开了逆转录病毒衍生载体，其中逆转录病毒包膜糖蛋白已经被水泡性口炎病毒的G糖蛋白替代，以及这些载体在将外源基因转移到多种非哺乳动物生物体的细胞中的用途。还公开了用于产生高滴度的逆转录病毒载体的方法，其中提供重组的稳定的宿主细胞系，其含有没有包膜蛋白的感兴趣的逆转录病毒载体。通过将编码功能性膜相关蛋白的核酸引入细胞系来启动高效价逆转录病毒载体产生。本申请中公开的载体可以通过超速离心浓缩至大于109cfu / ml的滴度，这在人类基因治疗试验中特别有用，并且还可以感染通常抗感染的细胞，例如仓鼠和鱼细胞含有逆转录病毒包膜蛋白的载体。

6. 发明授权

US06432705B1 Inducible expression system 失效
标题翻译：诱导表达系统
公开(公告)号：US06432705B1
公开(公告)日：2002-08-13
申请号：US09566660
申请日：2000-05-08
申请人： Jiing-Kuan Yee , Theodore Friedmann , Shin-Tai Chen
发明人： Jiing-Kuan Yee , Theodore Friedmann , Shin-Tai Chen
IPC分类号： C12N500
CPC分类号： C12N15/86 , C12N2740/13043 , C12N2830/002 , C12N2830/006 , C12N2840/20 , C12N2840/203
摘要： The present invention features compositions and methods for the inducible expression of a polypeptide, especially a polypeptide normally cytotoxic to the eukaryotic host cell in which it is to be expressed. A nucleotide sequence encoding a polypeptide of interest is operably linked to an inducible promoter. Expression from the inducible promoter is regulated by a multi-chimeric transactivating factor, composed of a first ligand-binding domain that negatively regulates transcription, a transcriptional activation domain, and a second ligand-binding domain that positively regulates the transcriptional activation function of the transactivator. Transcription of the nucleotide sequence under control of the inducible promoter is activated by the multi-chimeric transactivator when both the ligand that binds the first ligand-binding domain is absent and the ligand that binds the second ligand-binding domain is present. This inducible expression system is particularly useful in the expression of the cytotoxic protein VSV G for the production of pseudotyped retroviral vectors.
摘要翻译：本发明的特征在于可诱导表达多肽的组合物和方法，特别是对待其表达的真核宿主细胞通常具有细胞毒性的多肽。编码目的多肽的核苷酸序列与诱导型启动子可操作地连接。来自诱导型启动子的表达由多嵌合反式激活因子调节，所述多嵌合反式激活因子由负调节转录的第一配体结合结构域，转录激活结构域和正调节反式激活因子的转录激活功能的第二配体结合结构域组成。当两个结合第一配体结合结构域的配体和不存在结合第二配体结合结构域的配体时，多重嵌合反式激活剂可激活在诱导型启动子控制下的核苷酸序列的转录。这种诱导表达系统特别可用于细胞毒素蛋白VSV G的表达以产生假型逆转录病毒载体。

7. 发明授权

US5512421A Generation, concentration and efficient transfer of VSV-G pseudotyped retroviral vectors 失效
标题翻译： VSV-G假型逆转录病毒载体的产生，集中和有效转移
公开(公告)号：US5512421A
公开(公告)日：1996-04-30
申请号：US104804
申请日：1993-08-10
申请人： Jane C. Burns , Jiing-Kuan Yee , Theodore Friedmann
发明人： Jane C. Burns , Jiing-Kuan Yee , Theodore Friedmann
IPC分类号： C12N5/00 , A61K38/00 , A61K48/00 , C07K14/145 , C12N5/10 , C12N7/00 , C12N7/04 , C12N15/09 , C12N15/867 , C12N15/87 , C12R1/91 , C12N15/86 , C12N7/02 , C12N15/47 , C12N15/48
CPC分类号： C12N15/86 , A61K48/00 , C07K14/005 , C12N15/87 , C12N7/00 , A61K38/00 , C12N2740/13043 , C12N2740/13052 , C12N2740/13062 , C12N2760/20222 , C12N2830/002 , C12N2830/42 , C12N2830/60 , C12N2840/20 , C12N2840/203
摘要： The present application discloses retrovirus-derived vectors in which the retroviral envelope glycoprotein has been replaced by the G glycoprotein of vesicular stomatitis virus, and the use of these vectors in the transfer of exogenous genes into the cells of a wide variety of non-mammalian organisms. Also disclosed is a method for the generation of retroviral vectors in high titers, wherein a recombinant, stable host cell line is provided which harbors the retroviral vector of interest without envelope protein. High-titer retroviral vector production is initiated by introducing nucleic acid encoding a functional membrane-associated protein into the cell line. The vectors disclosed in the present application can be concentrated by ultracentrifugation to titers greater than 10.sup.9 cfu/ml which are especially useful in human gene therapy trials, and can also infect cells, such as hamster and fish cells, that are ordinarily resistant to infection with vectors containing the retroviral envelope protein.
摘要翻译：本申请公开了逆转录病毒衍生载体，其中逆转录病毒包膜糖蛋白已经被水泡性口炎病毒的G糖蛋白替代，以及这些载体在将外源基因转移到多种非哺乳动物生物体的细胞中的用途。还公开了用于产生高滴度的逆转录病毒载体的方法，其中提供重组的稳定的宿主细胞系，其含有没有包膜蛋白的感兴趣的逆转录病毒载体。通过将编码功能性膜相关蛋白的核酸引入细胞系来启动高效价逆转录病毒载体产生。本申请中公开的载体可以通过超速离心浓缩至大于109cfu / ml的滴度，这在人类基因治疗试验中特别有用，并且还可以感染通常抗感染的细胞，例如仓鼠和鱼细胞含有逆转录病毒包膜蛋白的载体。

8. 发明授权

US06451304B1 Method for retrovirus vector production by separated gag and pol expression 失效
标题翻译：通过分离的gag和pol表达产生逆转录病毒载体的方法
公开(公告)号：US06451304B1
公开(公告)日：2002-09-17
申请号：US09265013
申请日：1999-03-09
申请人： Theodore Friedmann , Atsushi Miyanohara
发明人： Theodore Friedmann , Atsushi Miyanohara
IPC分类号： A01N6300
CPC分类号： C12N15/86 , C12N2740/13043 , C12N2740/16043
摘要： The invention provides a system for production of retroviruses which are replication incompetent. In the system, gag and pol retroviral structural proteins are expressed separately by different plasmids in a packaging cell line. Separate gag and pol expressing plasmids are provided, as are packaging cell lines containing such plasmids. Retrovirus products of the retroviral vector production system, including chimeric retroviruses, are also provided.
摘要翻译：本发明提供了一种用于生产复制无能力的逆转录病毒的系统。在系统中，gag和pol逆转录病毒结构蛋白在包装细胞系中由不同质粒分开表达。提供单独的gag和pol表达质粒，以及含有这种质粒的包装细胞系也是如此。还提供了逆转录病毒载体生产系统的逆转录病毒产品，包括嵌合逆转录病毒。

9. 发明授权

US06171862B2 Transfection in serum-containing media 失效
标题翻译：含血清培养基中的转染
公开(公告)号：US06171862B2
公开(公告)日：2001-01-09
申请号：US09052797
申请日：1998-03-31
申请人： Akihiro Abe , Atsushi Miyanohara , Theodore Friedmann
发明人： Akihiro Abe , Atsushi Miyanohara , Theodore Friedmann
IPC分类号： C12N1587
CPC分类号： C12N15/87 , A61K48/00 , C12N15/88
摘要： Transfection of host cells cultured in the presence of serum is increased by adding VSV-G or polybrene to a nucleic acid-lipid complex or culture medium prior to transfection.
摘要翻译：在转染前，通过向核酸 - 脂质复合物或培养基中加入VSV-G或聚凝胺来增加在血清存在下培养的宿主细胞的转染。

10. 发明授权

US07060688B2 Products and methods for controlling the suppression of the neoplastic phenotype 失效
公开(公告)号：US07060688B2
公开(公告)日：2006-06-13
申请号：US10028726
申请日：2001-12-21
申请人： Wen-Hwa Lee , Huei-Jen Sue Huang , Eva Y. H. P. Lee , Theodore Friedmann , Jiing-Kuan Yee
发明人： Wen-Hwa Lee , Huei-Jen Sue Huang , Eva Y. H. P. Lee , Theodore Friedmann , Jiing-Kuan Yee
IPC分类号： A61K48/00 , A61K35/00
CPC分类号： C12N15/8509 , A01K67/0276 , A01K2217/05 , A01K2217/075 , A01K2227/105 , A01K2267/0331 , A61K38/00 , A61K48/00 , C07K14/47 , C07K16/18 , C12N9/16 , C12N2799/026 , G01N33/574
摘要： A method for gene therapy for cancers wherein chromosomal location of an inactive or defective cancer suppressing gene is established, a replacement gene which is preferably cloned is then used to replace the inactive or defective cancer suppressing gene in the chromosome. In addition to its uses in therapy, the present invention provides a means for prophylactically treating individuals having a genetic predisposition to cancer and provides an animal model for testing for carcinogenicity of environmental substances.

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